Tri-o-tolylphosphine → HCID 24891660, compound

HRID 1880019Notes

Reaction equation

HRID 1880019 reaction equation
Br[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][NH:10][C:4]=2[CH:3]=1.[CH3:13][N:14]([CH2:19][C:20]1[O:21][C:22]2[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=2[C:24]=1[CH3:25])[C:15](=[O:18])[CH:16]=[CH2:17].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][N:14]([CH2:19][C:20]1[O:21][C:22]2[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=2[C:24]=1[CH3:25])[C:15](=[O:18])/[CH:16]=[CH:17]/[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][NH:10][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 68412931HCID 68412931, compound

Product 1

HCID 24891660HCID 24891660, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 8-bromo-2,3,4,5-tetrahydro-1H-pyrido[2,3-b][1,4]diazepine (0.15 g, 0.66 mmol), N-methyl-N-((3-methyl benzofuran-2-yl)methyl)acrylamide (0.30 g, 1.32 mmol), (i-Pr)2EtN (0.34 mL, 2.0 mmol) in DMF (7 mL) was de-oxygenated with Ar for 30 min. Pd(OAc)2 (15 mg, 0.066 mmol) and P(o-tol)3 (40 mg, 0.13 mmol) was added and the solution was de-oxygenated for an additional 15 min. The reaction was heated to 100° C. for 18 hrs at which time the reaction was cooled to room temperature and then filtered through a short column of silica washing with EtOAc (20 mL). The filtrate was washed with brine (2×30 mL), dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 99:1) gave the title compound (111 mg, 45%) as a yellow powder; 1H NMR (400 MHz, DMSO-d6) δ 7.75 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.48 (d, J=7.6, 1H), 7.43 and 7.39 (2×s, 1H), 7.35-7.22 (m, 3H), 7.08 and 6.82 (2×d, J=15, 1H), 6.22 (s, 1H), 5.25 (s, 1H), 4.90 and 4.78 (2×s, 2H), 3.14-2.93 (m, 7H), 2.26 (s, 3H), 1.68 (m, 2H); ESI MS m/z 377 [C22H24N4O2+H]+

Workup

  1. temperaturewas cooled to room temperature
  2. filtrationfiltered through a short column of silica washing with EtOAc (20 mL)
  3. washThe filtrate was washed with brine (2×30 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 99:1)

Sources & evidence

ORD record
ord-44ed478ce7a84338a48eacc14266cccc
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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